Accurate diagnosis of solid pediatric tumors requires a combination of diagnostic techniques including reverse transcription polymerase chain reaction (RT-PCR). Many pediatric solid tumors exhibit fundamental cytogenetic abnormalities that have implications in their pathogenesis. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (RMS) are characterized by consistent chromosomal translocations which result in the fusion of genes and subsequent formation of novel chimeric genes. These molecular markers can be detected by RT-PCR or fluorescence in situ hybridization (FISH) and can be used not only to establish the diagnosis in difficult cases, but also to understand the pathogenesis of these tumors. Recently, the products of these fusion genes have become the target of vaccine therapies in newly established protocols in the Pediatric Oncology Branch (POB) at the NCI. The objective of this project is: (1) to provide state of the art diagnosis on tissue specimens from pediatric tumor patients participating in POB clinical trials (2) to evaluate the molecular pathology of protocol-related pediatric tumors (presence or absence of specific fusion transcripts) (3) to evaluate the significance of molecular markers in the diagnosis, classification and pathogenesis of pediatric sarcomas. The following accomplishments have been made in the last year: (1) A total of 120 pediatric tumor pathology reports were issued. (2) A total of 35 pediatric tumor molecular pathology reports were issued. (3) Four pediatric tumor pathology studies were published.